呼出氨气光声光谱检测及医学应用研究
|
摘要
人类呼出气中含有丰富的生理和疾病标志性信息,其中有多种组分可以作为疾病和代谢过程的“生物标记”。呼出气中氨气的产生与体内氮的代谢有关,它与血液中的血尿素氮(BUN)存在一定的线性关系,可以通过检测呼出气中氨气含量来诊断肾脏功能。基于光声光谱技术的呼出氨气检测系统具有灵敏度高、选择性好和操作简便等特点,可以实现呼出氨气的高灵敏度实时检测,进而对肾衰竭患者血液透析效果做出间接评价,本文在呼出氨气检测系统的实验模拟和临床应用方面进行了深入的研究。
首先介绍了呼出气检测的发展历史和各种分析技术及其特点,并分析了目前国内外呼出氨气的研究现状。在红外光谱产生原理的基础上阐述了光声光谱技术的基本理论和多组分气体检测方法。并针对呼出氨气的产生机理进行了分析,为呼出氨气检测用于临床医学诊断提供了理论依据。
为配合呼出气检测的特点和要求,在基于TEDFL和EDFA的光声光谱检测系统基础上,设计了小体积低表面能材料光声池,并增加了呼吸采气和恒温控制装置,研制出高灵敏度呼出氨气检测系统。采用多气体光谱测量算法,实现了高浓度CO2和H20存在条件下NH3的高灵敏度快速检测。采用标准气配制的模拟呼出气建立了呼出氨气的标定模型。
在理论和实验分析基础上,开展了针对多名健康志愿者和终末期肾病患者(ESRD)的呼出氨气检测实验。其中,健康志愿者的呼出氨气浓度在200ppb-500ppb之间；ESRD患者透析前呼出氨气浓度在2000ppb左右,透析过程中呼出氨气浓度呈下降趋势,前半个小时下降趋势显著,随后下降趋于平缓,透析结束时呼出氨气浓度维持在200-600ppb之间。测量结果显示,终末期肾病患者透析前后呼出氨气下降率(BARR)基本超过65%,与临床常用的BUN检测透析治疗充分性标准一致,说明我们研制的基于光声光谱技术的呼出氨气检测系统具备了临床血液透析过程疗效的实时监测能力,可以成为血液透析效果评价的一种新的技术手段。
Exhaled breath contains more than3000constituents at trace level concentrations, with a wide variety of these compounds potentially serving as biomarkers for specific diseases, physiologic status, or therapeutic progress. Breath ammonia in vivo comes from the nitrogenous metabolism, which has a good linear relationship with the blood urea nitrogen(BUN). The correlation between breath ammonia and BUN suggests that breath ammonia analysis have the potential to be an effective surrogate for BUN for monitoring haemodialysis(HD) efficacy. Photoacoustic spectroscopy can be used as a technique to measure real-time levels of ammonia in exhaled breath for its advantages such as high sensitivity, simultaneous and continuous measurement of multiple gases and so on. The paper is aimed at the theoretical and clinical experimental studies of breath ammonia monitoring based on photoacoustic trace gas detection technique, the main contents are as follows:
This thesis reviews the development history and technique of exhaled gas analysis, and introduces current status of breath ammonia detection study. On the base of gas absorption spectrum theory, the elementary principles of photoacoustic spectroscopy are discussed in detail, which includes the generation of photoacoustic signal and the technologies of wavelength modulation and harmonic detection. The mechanism and pathology of exhaled ammonia are discussed, which provide the theoretical basis for breath ammonia detection in the application of monitoring haemodialysis efficacy.
The photoacoustic spectrometer based on tunable erbium doped fiber laser(TEDFL)and erbium doped fiber amplifier(EDFA) was optimized to meet the requirement of breath gas detection, a photoacoustic cell with PTFE materials was designed, the temperature control system as well as a respiratory gas acquisition device was increased, a high performance breath ammonia analyzer based on photoacoustic trace gas detection technique was developed. Based on the algorithm of multi-gas measurement, the breath ammonia analyzer can detect breath ammonia with high sensitivity under the conditions of high concentrations of CO2and H2O. And then the simulated exhaled gas experiment was carried out in order to establish calibration models.
Based on the theory and experimental analysis of breath ammonia monitor, a clinical trial on the breath ammonia levels of several healthy volunteers and patients with end-stage renal disease(ESRD) in the hemodialysis process was carried out. The experiment of exhaled ammonia concentration in healthy volunteers yields an average level of breath ammonia of300ppb, ranging from200ppb to500ppb. And the breath ammonia levels in eight patients with ESRD while they were undergoing hemodialysis decline similar to the index trend in the dialysis process. The initial levels of breath ammonia at the beginning of dialysis are between1800ppb and2200ppb.These levels drop very sharply in the first30min intervals during the dialysis, the reduction in breath ammonia concentration is relatively slow from this point on to the end of dialysis treatment, at which point the levels taper off at200to600ppb, which close to the levels of healthy subjects. The decline rate of exhaled ammonia is more than65%, which is in agreement with the BUN test used in clinical dialysis. These preliminary data indicate that the breath ammonia analyzer has the clinical application value of the real-time monitoring of dialysis efficacy of ESRD patients and determining the endpoint of hemodialysis.
首先介绍了呼出气检测的发展历史和各种分析技术及其特点,并分析了目前国内外呼出氨气的研究现状。在红外光谱产生原理的基础上阐述了光声光谱技术的基本理论和多组分气体检测方法。并针对呼出氨气的产生机理进行了分析,为呼出氨气检测用于临床医学诊断提供了理论依据。
为配合呼出气检测的特点和要求,在基于TEDFL和EDFA的光声光谱检测系统基础上,设计了小体积低表面能材料光声池,并增加了呼吸采气和恒温控制装置,研制出高灵敏度呼出氨气检测系统。采用多气体光谱测量算法,实现了高浓度CO2和H20存在条件下NH3的高灵敏度快速检测。采用标准气配制的模拟呼出气建立了呼出氨气的标定模型。
在理论和实验分析基础上,开展了针对多名健康志愿者和终末期肾病患者(ESRD)的呼出氨气检测实验。其中,健康志愿者的呼出氨气浓度在200ppb-500ppb之间；ESRD患者透析前呼出氨气浓度在2000ppb左右,透析过程中呼出氨气浓度呈下降趋势,前半个小时下降趋势显著,随后下降趋于平缓,透析结束时呼出氨气浓度维持在200-600ppb之间。测量结果显示,终末期肾病患者透析前后呼出氨气下降率(BARR)基本超过65%,与临床常用的BUN检测透析治疗充分性标准一致,说明我们研制的基于光声光谱技术的呼出氨气检测系统具备了临床血液透析过程疗效的实时监测能力,可以成为血液透析效果评价的一种新的技术手段。
Exhaled breath contains more than3000constituents at trace level concentrations, with a wide variety of these compounds potentially serving as biomarkers for specific diseases, physiologic status, or therapeutic progress. Breath ammonia in vivo comes from the nitrogenous metabolism, which has a good linear relationship with the blood urea nitrogen(BUN). The correlation between breath ammonia and BUN suggests that breath ammonia analysis have the potential to be an effective surrogate for BUN for monitoring haemodialysis(HD) efficacy. Photoacoustic spectroscopy can be used as a technique to measure real-time levels of ammonia in exhaled breath for its advantages such as high sensitivity, simultaneous and continuous measurement of multiple gases and so on. The paper is aimed at the theoretical and clinical experimental studies of breath ammonia monitoring based on photoacoustic trace gas detection technique, the main contents are as follows:
This thesis reviews the development history and technique of exhaled gas analysis, and introduces current status of breath ammonia detection study. On the base of gas absorption spectrum theory, the elementary principles of photoacoustic spectroscopy are discussed in detail, which includes the generation of photoacoustic signal and the technologies of wavelength modulation and harmonic detection. The mechanism and pathology of exhaled ammonia are discussed, which provide the theoretical basis for breath ammonia detection in the application of monitoring haemodialysis efficacy.
The photoacoustic spectrometer based on tunable erbium doped fiber laser(TEDFL)and erbium doped fiber amplifier(EDFA) was optimized to meet the requirement of breath gas detection, a photoacoustic cell with PTFE materials was designed, the temperature control system as well as a respiratory gas acquisition device was increased, a high performance breath ammonia analyzer based on photoacoustic trace gas detection technique was developed. Based on the algorithm of multi-gas measurement, the breath ammonia analyzer can detect breath ammonia with high sensitivity under the conditions of high concentrations of CO2and H2O. And then the simulated exhaled gas experiment was carried out in order to establish calibration models.
Based on the theory and experimental analysis of breath ammonia monitor, a clinical trial on the breath ammonia levels of several healthy volunteers and patients with end-stage renal disease(ESRD) in the hemodialysis process was carried out. The experiment of exhaled ammonia concentration in healthy volunteers yields an average level of breath ammonia of300ppb, ranging from200ppb to500ppb. And the breath ammonia levels in eight patients with ESRD while they were undergoing hemodialysis decline similar to the index trend in the dialysis process. The initial levels of breath ammonia at the beginning of dialysis are between1800ppb and2200ppb.These levels drop very sharply in the first30min intervals during the dialysis, the reduction in breath ammonia concentration is relatively slow from this point on to the end of dialysis treatment, at which point the levels taper off at200to600ppb, which close to the levels of healthy subjects. The decline rate of exhaled ammonia is more than65%, which is in agreement with the BUN test used in clinical dialysis. These preliminary data indicate that the breath ammonia analyzer has the clinical application value of the real-time monitoring of dialysis efficacy of ESRD patients and determining the endpoint of hemodialysis.
引文
[I]T. H. Risby, S. F. Solga. Current Status of Clinical Breath Analysis[J]. Applied Physics B.2006,85(2-3):421-426.
[2]S. Y. Tan, M. Hu. Medicine in Stamps Antoine-Laurent Lavoisier (1743-1794):Founder of Modern Chemistry[J]. Singapore Medical Journal.2004,45(7):303-304.
[3]J. S. Haldane, J. G. Priestley. The regulation of the lung ventilation[J]. J Physiol. 1905,32(3-4):225-266.
[4]D. J. Morgan. Construction and Operation of a Simple Flame-Ionization Detector for Gas Chromatography[J]. Journal of Scientific Instruments.1961,38(12):501-503.
[5]D. H. Calloway, D. J. Colasito, R. D. Mathews. Gases Produced by Human Intestinal Microflora[J]. Nature Nanotechnology.1966,212:1238-1239.
[6]M. D. Levitt. Production and Excretion of Hydrogen Gas in Man[J]. New England Journal of Medicine.1969,281:122-126.
[7]L. Pauling, A. B. Robinson, Teranish. R, et al. Quantitative Analysis of Urine Vapor and Breath by Gas-Liquid Partition Chromatography[J]. Proceedings of the National Academy of Sciences of the United States of America.1971,68:2374-2376.
[8]K. M. Paschke, A. Mashir, R. A. Dweik. clinical applications of breath testing[J]. F1000 Medicine Reports.2010,2(56):1-6.
[9]S. M. Gordon, J. P. Szidon, B. K. Krotoszynski,et al. Volatile organic compounds in exhaled air from patients with lung cancer[J]. Clin Chem.1985,31(8):1278-1282.
[10]J. Yu,H. Byun, M. So, et al. Analysis of diabetic patient's breath with conducting polymer sensor array[J]. Sensors and Actuators B:Chemical.2005,108:305-308.
[11]D. Pantoflickova, D. Scott, G. Sachs, et al.13C urea breath test (UBT) in the diagnosis of Helicobacter pylori:why does it work better with acid test meals[J]. British Medical Journal.2003,52(7):933-937.
[12]L. E. Gustafsson. Exhaled nitric oxide as a marker in asthma[J]. Eur Respire J Suppl.1998,26:49-52.
[13]D. H. Yates. Role of exhaled nitric oxide in asthma[J]. Immunol Cell Biol.2001,79 (2):178-90.
[14]E. Aghdassi, J. P. Allard. Breath alkanes as a marker of oxidative stress in different clinical conditions[J]. Free Radic Biol Med.2000,28:880-886.
[15]张晨,人体呼出气中挥发性有机化合物的检测方法[J].化学进展.2010,22(1)：140-147.
[16]Anton Amann, Patrik spanel, David Smith. Breath Analysis:The Approach Towards Clinical Applications[J]. Mini-Reviews in Medicinal Chemistry.2007,7:115-129.
[17]N.M.Audrey, R. F. George. Human breath analysis:methods for sample collection and reduction of localized background effects[J]. Anal Bilanal Chem.2010,3(96): 739-750.
[18]J. D. Pleil, A. B. Lindstrom. Exhaled human breath measurement method for assessing exposure to halogenated volatile organic compounds[J]. Clinical Chemistry.1997 43:723-730.
[19]M. Giardina, S. V. Olesik. Application of low-temperature glassy carbon-coated macrofibers for solid-phase microextraction analysis of simulated breath volatiles[J]. Analytical Chemistry.2003,75 (7):1604-1614.
[20]J. M. Sanchez, R. D. Sacks. GC analysis of human breath with a series-coupled column ensemble and a multibed sorption trap[J]. Analytical Chemistry.2003,75:2231-2236.
[21]H. Lord, Y. F. Yu, A. Segal, and J. Pawliszyn, Breath analysis and monitoring by membrane extraction with sorbent interface[J]. Analytical Chemistry.2002, 74 (21):5650-5657.
[22]Patrik Spanel, David Smith. Progress in SIFT-MS-.breath analysis and other application[J]. Mass Spectrometry Reviews.2011,30:236-267
[23]J Beauchamp, F Kirsch, A Buettner. Real-time breath gas analysis for pharmacokinetics:monitoring exhaled breath by on-line proton-transfer-reaction mass spectrometry after ingestion of eucalyptol-containing capsules[J]. J. Breath Res.2010,4.
[24]D. Smith, P. Spanel. The novel selected ion flow tube approach trace gas analysis of air and breath[J]. Rapid Communications in Mass Spectrometry.1996,10:1183-1198.
[25]B. M. Ross. Sub-parts per billion detection of trace volatile chemicals in human breath using Selected Flow Tube Mass Spectrometry[J]. BioMed Central.2008,1:41.
[26]Z H Endre, J W Pickering. Breath ammonia and trimethylamine allow real-time monitoring of haemodialysis efficacy[J]. Physiological Measurement.2011,32(1): 115-130
[27]Wolfgang Singer, Jens Herbig, Rene Gumann. Applications of PTR-MS in Medicine and Biotechnology[J]. Life Science Solutions.2011
[28]Ulrich Riess, Uwe Tegtbur. Experimental setup and analytical methods for the non-invasive determination of volatile organic compounds, formaldehyde and NOx in exhaled human breath[J]. Analytica Chimica Acta.2010,53-62
[29]J King, PMochalski. Dynamic profiles of volatile organic compounds in exhaled breath as determined by a coupled PTR-MS/GC-MS study[J]. Physiol. Meas.2010,31: 1169-1184
[30]K. Okamura, T. Ishi ji, M. Iwaki, Y. Suzuki, K. Takahashi. Electrochemical gas sensor using a novel gas permeable electrode modified by ion implantation [J]. Surface and Coatings Technology.2007,201:8116-8119.
[31]A. D.Wilson, M. Baietto. Advances in Electronic-Nose Technologies Developed for Biomedical Applications[J]. Sensors.2011,11:1105-1176.
[32]Reinhard Fend, et al. Monitoring haemodialysis using electronic nose and chemometrics[J]. Biosensors and Bioelectronics,2004,119:1581-1590
[33]Haick H, Hakim M, Patrascu M, Levenberg C, Shehada N, Nakhoul F, Abassi Z. Sniffing chronic renal failure in rat model by an array of random networks of single-walled carbon nanotubes[J]. ACS Nano.2009,3(5):1258-1266
[34]P. Montuschi, M. Santonico. Diagnose performance of an electronic nose, fractional exhaled nitric oxide and lung function testing in asthma[J]. Chest 2010,137, 790-796.
[35]Perena Gouma, Krithika Kalyanasundaram, Xiao Yun. Nanosensor and Breath Analyzer for Ammonia Detection in Exhaled Human Breath [J]. IEEE SENSORS JOURNAL.2010,10(1): 49-53.
[36]V. H. Tran, P. C. Hiang, M. Thurston, P. S. Thomas, et al. Breath analysis of lung cancer patients using an electronic nose detection system[J]. IEEE Sens. J.2010, 10 (9):1514-1518.
[37]Wang Ping, Tan Yi, et al. A novel method for diabetes diagnosis based on electronic nose [J]. Biosensors & Bioelectronics.1997,12 (9-10):1031～1036
[38]胡卫军,王平,杨成忠,胥媛.仿生光学人工鼻及其呼吸气体检测的实验研究[J].中国生物医学工程学报,2006,25(1)：51-57
[39]王乐,王镝,王平.基于谐振型SAW传感器的呼吸监测系统设计[J].传感技术学报,2011,24(4)：498-502
[40]S. Persijn, F. Harren, A.vanderVeen. Quantitative gas measurements using a versatile OPO-based cavity ringdown spectrometer and the comparison with spectroscopic databases[J]. Appl. Phys. B.2010,100(2):383-390.
[41]J. Wojtas, Z. Blelecki, T. Stacewicz, J. Stacewicz, Ultra sensitive laser spectroscopy for breath analysis. Opto-Electron. Rev.2012.20(1):26-39.
[42]V. Spagnolo, A. A. Kosterev, L. Dong, R. Lewicki, F. K. Tittel. NO trace gas sensor based on quartz-enhanced photoacoustic spectroscopy and external cavity quantum cascade laser[J]. Appl. Phys. B.2010,100(1):125-130.
[43]F. J. M. Harren, R. Berkelmans, K. Kuiper, S. te Lintel Hekkert, P. Scheepers, R. Dekhuijzen. On-line laser photoacoustic detection of ethane in exhaled air as biomarker of ultraviolet radiation damage of the human skin[J]. Applied Physics Letters,1999,74(12):1761-1763.
[44]C. Roller, K. Namjou, J. Jeffers, et al. Simultaneous NO and C02 measurement in human breathwith a single IV-VImid-infrared laser[J]. Optics Letters.2002, 27 (2):107-109.
[45]C. Roller, K. Namjou, J. D. Jeffers,et al. Nitric oxide breath testing by tunable-diode laser absorption spectroscopy:Application in monitoring respiratory inflammation[J]. Applied Optics.2002,41 (28):6018-6029.
[46]M. M. Baum, S. Kumar, A. M. Lappas, et al. Measurement of acetylene in breath by ultraviolet absorption spectroscopy:Potential for noninvasive cardiac output monitoring[J]. Review of Scientific Instruments.2003,74(6):3104-3110.
[47]C. J. Wang, S. T. Scherrer, D. Hossain. Measurements of cavity ringdown spectroscopy of acetone in the ultraviolet and near-infrared spectral regions:Potential for development of a breath analyzer[J].Applied Spectroscopy.2004,58(7):784-791.
[48]K. D. Skeldon, C. A. Wyse, S. D. Monk. Application of laser spectroscopy for measurement of exhaled ethane in patients with lung cancer [J]. Respiratory Medicine.2006,100 (2): 300-306.
[49]T. Hibbard, A. J. Killard. Breath ammonia level in a normal human population study as determined by photoacoustic laser spectroscopy[J]. Journal of Breath Research. 2011,5(3):1-8.
[50]D. D. Arslanov, Koen Swinkels, S. M. Cristescu, F. J. M. Harren. Real-time, subsecond, multicomponent breath analysis by Optical Parametric Oscillator based Off-Axis Integrated Cavity Output Spectroscopy [J]. Opt Express.2011,19(24)-.24078-24089.
[51]C. Patel. Sensitive Analysis of Breath Gases for "Bloodless Blood Tests" [J]. Gases and Technology,2002,1:24-30.
[52]C. Kumar Patel, Eric Mueller. Optical-nose technology competes with breath analyzers and blood test[J]. Laser Focus With Fiberoptic Technology.2002,38(11) 83-84,86,88.
[53]Hibbard, Troy, Killard, Anthony. Breath ammonia analysis:Clinical application and measurement[J]. Critical Reviews in Analytical Chemistry.2011,41(1):21—35.
[54]Hiroyuki Wakabayashi, Yoshihiro Kuwabara, Hiroyuki Murata,et al. Measurement of the Expiratory Ammonia Concentration and its Clinical Significance [J]. Metabolic Brain Disease.1997,12(2):161-169.
[55]S. Davies, P. Spanel, D. Smith. Quantitative analysis of ammonia on the breath of patients in end-stage renal failure [J]. Kidney International.1997,52:223-228.
[56]Ricardo Claps, F. V. Englich, F. K. Tittel, et al. Ammonia detection by use of near-infrared diode-laser-based overtone spectroscopy[J]. Applied Optic.2001, 40(24):4387-4394.
[57]L. Narasimhan, W. Goodman, C. Patel. Correlation of breath ammonia with blood urea nitrogen and creatinine during hemodialysis [J], Proceedings of the National Academy of Sciences of the United States of America,2001,98:4617-4621.
[58]Kearney D J, Hubbard T, Putnam D. Breath Ammonia Measurement in Helicobacter pylori Infection[J]. Digestive Diseases and Sciences.2002,47(11):2523-2530.
[59]A. M. Diskin, P. Spanel, D. Smith. Time variation of ammonia, acetone, isoprene and ethanol in breath:a quantitative SIFT-MS study over 30 days [J]. Physiological Measurement.2003,24:107-119.
[60]Suja DuBois, Sue Eng, Renuka Bhattacharya, et al. Breath Ammonia Testing for Diagnosis of Hepatic Encephalopathy[J]. Digestive Diseases and Sciences.2005, 50(10):1780-1784.
[61]Kei Toda, Jianzhong Li, Purnendu K. Dasgupta. Measurement of ammonia in human breath with a liquid-film conductivity sensor[J]. Anal. Chem.2006,78:7284-7291.
[62]J. Manne,0. Sukhorukov, W. Jager, J. Tulip. Pulsed quantum cascade laser-based cavity ring-down spectroscopy for ammonia detection in breath[J], Applied Optics, 2006,45:9230-9237
[63]Patrik Spanel, Kseniya Dryahina, David Smith. Acetone, ammonia and hydrogen cyanide in exhaled breath of several volunteers aged 4-83 years [J]. J. Breath Res. 2007,1(1):1-4.
[64]H. Ishida, T. Satou, K. Tsu ji, N. Kawashima, H. Takemura, Y. Kosaki, S. Shiratori, T. Agishi. The breath ammonia measurement of the hemodialysis with a QCM-NH3 sensor[J]. Bio-Medical Materials and Engineering.2008,18:99-106.
[65]Katherine T. Moorhead. Modelling Acute Renal Failure using Blood and Breath Biomarkers inRats[J]. The 7th IFAC Symposium on Modelling and Control inBiomedical Systems.2009.144-150
[66]P. Gouma, K. Kalyanasundaram, X. Yun, M. Stanacevic, L. S. Wang. Nanosensor and Breath Analyzer for Ammonia Detection in Exhaled Human Breath[J]. IEEE Sensors Journal. 2010,10:49-53.
[67]D. C. Dumitras, D. C. Dutu, C. Matei, et al. Evaluation of Ammonia Absorption Coefficients by Photoacoustic Spectroscopy for Detection of Ammonia Levels in Human Breath[J]. Laser Physics.2001,214:796-800.
[68]Giovanni Neri, Antonio Lacquaniti,Giuseppe Rizzo. Real-time monitoring of breath ammonia during haemodialysis:use of ion mobility spectrometry(IMS) and cavity ring-down spectroscopy(CRDS) techniques[J]. Nephrology Dialysis Transplantation. 2012,0:1-8.
[69]A. G. Bell. On the production and reproduction of sound by light[J]. Am. J. Sci. 1880,20:305-324.
[70]M. L. Viegerov. Eine Methode der GAsanalyse, Beruhend auf der Optisch-Akustischen Tyndall-Rontegeners-cheinung[J].Dokl. Akad. Nauk SSSR.1938,19:687-688.
[71]K. Luft. Uber eine neue methode der registrierenden gasanalyse mit hilfe der absorption ultraroter strahlen ohne spektrale zerlegung[J]. Zeitschrift Fur Technische Physik.1943,24:97-104.
[72]G. Gorelik. On a possible method of studying energy exchange times between the different degrees of freedom of molecules in a gas [J]. Dokl. Akad. Nauk SSSR,1946, 54:779.
[73]E. L. Kerr, J.G. Atwood. The Laser Illuminated Absorptivity Spectrophone:A Method for Measurement of Weak Absorptivity in Gases at Laser Wavelengths[J], Applied Optics,1968,7:915-921.
[74]L. B. Kreuzer. Ultralow gas concentration infrared absorption spectroscopy[J]. Journal of Applied Physics.1971,42:2934.
[75]C. N. Patel, E. G. Burkhardt, C. A. Lambert. Spectroscopic Measurements of Stratospheric Nitric Oxide and Water Vapor[J]. Science.1974,184:1173-1176.
[76]张望.光声光谱微量气体检测技术及其应用研究[D]：(博士学位论文).大连：大连理工大学,2010.
[77]F. G. C. Bijnen, J. Reuss, F. J. M. Harren. Geometrical optimization of a longitudinal resonant photoacoustic cell for sensitive and fast trace gas detection[J]. Review of Scientific Instruments.1996,67:2914-2923.
[78]M. A. Gondal. Laser photoacoustic spectrometer for remote monitoring of atmospheric pollutants [J]. Applied Optics.1997,36:3195-3201.
[79]M. W. Sigrist, A. Bohren, T. von Lerber, et al. Environmental applications of laser-based photoacoustic spectroscopy[J]. Analytical Sciences.2001, 17:S511-S514.
[80]D. Marinov, M. W. Sigrist. Monitoring of road-traffic emissions with a mobile photoacoustic system [J]. Photochemical & Photobiological Sciences.2003,2:774-778.
[81]M. Gianella, J. M. Rey, D. Hahnloser, M. W. Sigrist. C02 laser-photoacoustic analysis of smoke emitted during minimal invasive electro-knife surgery[J]. Eur. Phys. J.2008, Special Topics 153,459-462.
[82]http://www.pranalytica.com/technology-gas-sensors
[83]M. B. Pushkarsky, M.E.Webber, C. K. N. Patel. Ultra-sensitive ambient ammonia detection using C02-laser-based photoacoustic spectroscopy[J]. Applied Physics B-Lasers and Optics.2003,77:381-385.
[84]http://www.ru.nl/tracegasfacility/trace_gas_research/laser_spectroscopy/
[85]S. M. Cristescu, S. T. Persuijn, S. TE Lintel Hekkert, F. J. M. Harren. Laser-based system for trace gas detection in life sciences. Appl. Phys. B.2008,92:343-349.
[86]F. Kuhnemann, K. Schneider, A. Hecker, A. Martis, W. Urban, S. Schiller, J. Mlynek. Photoacoustic trace-gas detection using a cw single-frequency parametric oscillator[J]. Applied Physics B:Lasers and Optics,1998,66:741-745.
[87]C. Fischer, M. Sigrist, Q. Yu, M. Seiter. Photoacoustic monitoring of trace gases by use of a diode-based difference frequency laser source [J]. Optics Letters,2001, 26:1609-1611
[88]T. L. Wee.J. Ng, A. H. Kung, A. Miklos, P. Hess. Trace gas detection of C2H4 by photoacoustic spectroscopy using a compact pulsed optical parametric oscillator [J].J. Phys. IV France.2005,125:597-599
[89]D. D. Arslanov, K. Swinkels, S. M. Cristescu, F. J. M. Harren. Real-time, subsecond, multicomponent breath analysis by Optical Parametric Oscillator based Off-Axis Integrated Cavity Output Spectroscopy[J].Opt. Express.2011,19:24078-24089.
[90]Z. Bozoki, A. Mohacsi, G. Szabo, Z. Bor, M. Erdelyi, W. D. Chen, F. K. Tittel. Near-infrared diode laser based spectroscopic detection of ammonia:A comparative study of photoacoustic and direct optical absorption methods [J], Applied Spectroscopy,2002,56:715-719.
[91]A. Schmohl, A. s. M. s, P. Hess. Detection of ammonia by photoacoustic spectroscopy with semiconductor lasers[J]. Applied Optics.2002,41:1815-1823.
[92]M. E. Webber, M. Pushkarsky, C. K. N. Patel. Fiber-amplifier-enhanced photoacoustic spectroscopy with near-infrared tunable diode lasers[J]. Applied Optics,2003,42:2119-2126.
[93]J. P. Besson, S. Schilt, L. Thevenaz. Sub-ppb ammonia detection based on photoacoustic spectroscopy [J].17th International Conference on Optical Fibre Sensors, Pts 1 and 2,2005,5855:415-418.
[94]Rafat Lewicki, Anatoliy A. Kosterev, David M. Thomazy, F. K. Titte. Real Time Ammonia Detection in Exhaled Human Breath using a distributed feedback quantum cascade laser based sensor [J]. Proc.of SPIE.2011,7945:50K-2
[95]B. A. Paldus, T. G. Spence, R. N. Zare, J. Oomens, F. J. M. Harren. Photoacoustic spectroscopy using quantum-cascade lasers [J], Optics Letters,1999,24:178-180.
[96]A. Mukherjee, M. Prasanna, M. Lane, R. Go, I. Dunayevskiy, A. Tsekoun, C. K. N. Patel. Optically multiplexed multi-gas detection using quantum cascade laser photoacoustic spectroscopy [J], Applied Optics,2008,47:4884-4887
[97]V. Spagnolo, A. A. Kosterev, L. Dong, R. Lewicki, F. K. Tittel. NO trace gas sensor based on quartz enhanced photoacoustic spectroscopy and external cavity quantum cascade laser[J]. App. Phys.B.2010,100:125-130.
[98]A. A. Kosterev, Y. A. Bakhirkin, R. F. Curl, F. K. Tittel. Quartz-enhanced photoacoustic spectroscopy [J], Optics Letters,2002,27:1902-1904.
[99]A. A. Kosterev, F. K. Tittel. Ammonia detection by use of quartz-enhanced photoacoustic spectroscopy with a near-IR telecommunication diode laser [J], Applied Optics,2004,43:6213-6217.
[100]Raf at Lewicki, A. A. Kosterev, Y. A. Bakhirkin, D. M. Thomazy, F. K. Titte, et al. Real Time Ammonia Detection in Exhaled Human Breath with a Quantum Cascade Laser Based Sensor[J]. Conference on Lasers and Electro-Optics (CLEO).2009.
[101]L. Dong,A. A. Kosterev, D. Thomazy, F. K. Tittel. Compact Portable QEPAS Multi-gas Sensor[J]. Proc. of SPIE.2011,7945:50R-1.
[102]J. Fonsen, V. Koskinen, K. Roth, J. Kauppinen. Dual cantilever enhanced photoacoustic detector with pulsed broadband IR-source[J]. Vibrational Spectroscopy.2009,50(2):214-217.
[103]C. B. Hirschmann, N. S. Koivikko, J. Raittila, et al. FT-IR-cPAS—New Photoacoustic Measurement Technique for Analysis of Hot Gases:A Case Study on VOCs[J]. Sensors(Basel).2011,11(5):5270-5289.
[104]C. N. Patel. Laser Photoacoustic Spectroscopy Helps Fight Terrorism:High Sensitivity Detection of Chemical Warfare Agent and Explosives[J]. The European Physical Journal.2008,Special Topics 153:1-18.
[105]http://www. omnisens.ch/vl/tga/251-tgaproducts. php
[106]http://www. innova-airtech. com/
[107]Liusan Wang, Zhensong Cao, Xiaoming Gao,et al.A widely tunable(5-12.5u m) continuous-wave mid-infrared laser spectrometer based on difference frequency generation in AgGaS2[J]. Optics Communications.2011,284:358-362.
[108]JingsongLi, X. Gao, W. Li, et al. Near-infrared diode laser wavelength modulation-based photoacoustic spectrometer[J]. Spectrochimica Acta Part A.2006, 64:338-342.
[109]K.Liu, J. Li, L. Wang, F. K. Tittel. Trace gas sensor based on quartz tuning fork enhanced laser photoacoustic spectroscop [J].Appl Phys B.2009,94:527-533.
[110]Hongming Yi, Kun Liu, Weidong Chen, et al. Application of a broadband blue laser diode to trace N02 detection using off beam quartz enhanced photoacoustic spectroscopy[J]. Optics Letters.2011,36(4):481-483.
[111]于清旭,王艺,刘中凡,林钧岫.双能级跃迁cO激光器腔内光声光谱测量[J].大连理工大学学报.1995,35：258-262.
[112]于清旭,林钧岫,尤斯·欧文斯,弗朗·斯哈伦.用激光光声检测技术研究乙醛对苹果乙烯产量的影响[J].大连理工大学学报.1999,39：498-503.
[113]Y. Peng, W. Zhang, L. Li, Q. X. Yu. Tunable fiber laser and fiber amplifier based photoacoustic spectrometer for trace gas detection[J]. Spectrochimica Acta Part a-Molecular and Biomolecular Spectroscopy.2009,74:924-927.
[114]刘善峥,张望,于清旭.基于可调谐掺铒光纤激光器和掺铒光纤放大器的光声光谱气体分析仪[J].中国激光.2009,36：964-967.
[115]Q. Y. Wang, J. W. Wang, Q. X. Yu. An all-optical photoacoustic spectrometer for trace gas detection[J]. Sensors and Actuators B-Chemical.2011,153:214-218.
[116]李洪艳.基于光声光谱技术的多组分气体检测系统研究[D].秦皇岛：燕山大学电气工程学院,2010.
[117]陈伟根,周恒逸,黄会贤,唐炬.基于半导体激光器的乙炔气体光声光谱检测及其定量分析[J].仪器仪表学报.2010,31(3)：665-670.
[118]王建业,纪新明,黄宜平等.光声光谱法探测微量气体[J].传感技术学报.2006,19(4)：1206-1211.
[119]http://www. xmzsh. com/.../2011年世界肾脏日宣传册(中华医学会肾脏病学分会编).doc
[120]肖月,隋宾艳,赵琨.我国终末期肾病现状及透析技术的应用、费用及支付情况分析[J].中国卫生政策研究.2011,4：29-33.
[121]USRDS 2011 Annual Data Report:Atlas of Chronic Kidney Disease and End-Stage Renal Disease in the United States, National Institutes of Health[R]. National Institute of Diabetes and Digestive and Kidney Diseases,2011.
[122]A. Singla, M. J. Antonino, K. P. Bliden,et al.The relation between platelet reactivity and glycemic control in diabetic patients with cardiovascular disease on maintenance aspirin and clopidogrel therapy[J]. American Heart Journal.2009, 158:784-784.
[123]Ligor,Tomasz. Analytical Methods for Breath Investigation[J]. Critical Reviews in Analytical Chemistry.2009,39(1):2-12
[124]A. Amann, et al. Breath analysis for medical diagnosis and therapeutic monitoring[J]. Spectroscopy Europe.2005,17(3):18-20.
[125]王宗明,何欣翔,孙殿卿.实用红外光谱学[M]：石油工业出版社,1990.
[126]李民赞.光谱分析技术及其应用[M]：科学出版社,2006.
[127]周炳琨,陈倜嵘.激光原理[M]：国防工业出版社,2009.
[128]陆同兴,路轶群.激光光谱技术原理及应用[M]：中国科学技术大学出版社,1999.
[129]J. P. BESSON. Photoacoustic spectroscopy for multi-gas sensing using near infrared lasers[D]. Lausanne:Swiss Federal Institute of Technology(EPFL),2006.
[130](美国)罗森威格著,王耀俊等译.光声学和光声谱学[M].北京：科学出版社,1986.
[131]殷庆瑞等著.光声光热技术及其应用[M].北京：科学出版社,1991
[132]刘善峥.基于光纤激光器和光纤放大器的光声光谱仪[D]：(硕士学位论文).大连：大连理工大学,2009.
[133]J. Reid, D. Labrie. Second-harmonic detection with tunable diode lasers—Comparison of experiment and theory[J]. Applied Physics B:Lasers and Optics.1981, 26(3):203-210.
[134]杨晓龙.光声光谱技术中的多气体成份分析方法研究[D]：(硕士学位论文).大连：大连理工大学,2003.
[135]张嵩.基于光声光谱技术的多组分气体检测方法研究[D]：(硕士学位论文).重庆：重庆大学,2007.
[136]P. G. Blake. Practical guide to measuring adequacy of dialysis [J]. Advances in renal replacement therapy.1999,6(1):80-84.
[137]J. S.Lee循环与呼吸系统中的物质传输[M]：重庆大学出版社,1993.
[138]李良.人体呼出氨气的光声光谱检测技术研究[D]：(硕士学位论文).大连：大连理工大学,2010.
[139]杨乐平,李海涛,肖相生.LabView程序程序设计与应用[M].北京：电子工业出版社,2005.
[140]Herzberg G.分子光谱与分子结构[M].北京：科学出版社,1983.
[141]HITRAN and PNNL Database, http://savi. weber. edu/hi_plot/index. html
[142]M. E. Webber, D. S. Baer, R. K. Hanson. Ammonia monitoring near 1.5μm with diode-laser absorption sensors[J].Applied Optics.2001,40(12):2031-2042.
[2]S. Y. Tan, M. Hu. Medicine in Stamps Antoine-Laurent Lavoisier (1743-1794):Founder of Modern Chemistry[J]. Singapore Medical Journal.2004,45(7):303-304.
[3]J. S. Haldane, J. G. Priestley. The regulation of the lung ventilation[J]. J Physiol. 1905,32(3-4):225-266.
[4]D. J. Morgan. Construction and Operation of a Simple Flame-Ionization Detector for Gas Chromatography[J]. Journal of Scientific Instruments.1961,38(12):501-503.
[5]D. H. Calloway, D. J. Colasito, R. D. Mathews. Gases Produced by Human Intestinal Microflora[J]. Nature Nanotechnology.1966,212:1238-1239.
[6]M. D. Levitt. Production and Excretion of Hydrogen Gas in Man[J]. New England Journal of Medicine.1969,281:122-126.
[7]L. Pauling, A. B. Robinson, Teranish. R, et al. Quantitative Analysis of Urine Vapor and Breath by Gas-Liquid Partition Chromatography[J]. Proceedings of the National Academy of Sciences of the United States of America.1971,68:2374-2376.
[8]K. M. Paschke, A. Mashir, R. A. Dweik. clinical applications of breath testing[J]. F1000 Medicine Reports.2010,2(56):1-6.
[9]S. M. Gordon, J. P. Szidon, B. K. Krotoszynski,et al. Volatile organic compounds in exhaled air from patients with lung cancer[J]. Clin Chem.1985,31(8):1278-1282.
[10]J. Yu,H. Byun, M. So, et al. Analysis of diabetic patient's breath with conducting polymer sensor array[J]. Sensors and Actuators B:Chemical.2005,108:305-308.
[11]D. Pantoflickova, D. Scott, G. Sachs, et al.13C urea breath test (UBT) in the diagnosis of Helicobacter pylori:why does it work better with acid test meals[J]. British Medical Journal.2003,52(7):933-937.
[12]L. E. Gustafsson. Exhaled nitric oxide as a marker in asthma[J]. Eur Respire J Suppl.1998,26:49-52.
[13]D. H. Yates. Role of exhaled nitric oxide in asthma[J]. Immunol Cell Biol.2001,79 (2):178-90.
[14]E. Aghdassi, J. P. Allard. Breath alkanes as a marker of oxidative stress in different clinical conditions[J]. Free Radic Biol Med.2000,28:880-886.
[15]张晨,人体呼出气中挥发性有机化合物的检测方法[J].化学进展.2010,22(1)：140-147.
[16]Anton Amann, Patrik spanel, David Smith. Breath Analysis:The Approach Towards Clinical Applications[J]. Mini-Reviews in Medicinal Chemistry.2007,7:115-129.
[17]N.M.Audrey, R. F. George. Human breath analysis:methods for sample collection and reduction of localized background effects[J]. Anal Bilanal Chem.2010,3(96): 739-750.
[18]J. D. Pleil, A. B. Lindstrom. Exhaled human breath measurement method for assessing exposure to halogenated volatile organic compounds[J]. Clinical Chemistry.1997 43:723-730.
[19]M. Giardina, S. V. Olesik. Application of low-temperature glassy carbon-coated macrofibers for solid-phase microextraction analysis of simulated breath volatiles[J]. Analytical Chemistry.2003,75 (7):1604-1614.
[20]J. M. Sanchez, R. D. Sacks. GC analysis of human breath with a series-coupled column ensemble and a multibed sorption trap[J]. Analytical Chemistry.2003,75:2231-2236.
[21]H. Lord, Y. F. Yu, A. Segal, and J. Pawliszyn, Breath analysis and monitoring by membrane extraction with sorbent interface[J]. Analytical Chemistry.2002, 74 (21):5650-5657.
[22]Patrik Spanel, David Smith. Progress in SIFT-MS-.breath analysis and other application[J]. Mass Spectrometry Reviews.2011,30:236-267
[23]J Beauchamp, F Kirsch, A Buettner. Real-time breath gas analysis for pharmacokinetics:monitoring exhaled breath by on-line proton-transfer-reaction mass spectrometry after ingestion of eucalyptol-containing capsules[J]. J. Breath Res.2010,4.
[24]D. Smith, P. Spanel. The novel selected ion flow tube approach trace gas analysis of air and breath[J]. Rapid Communications in Mass Spectrometry.1996,10:1183-1198.
[25]B. M. Ross. Sub-parts per billion detection of trace volatile chemicals in human breath using Selected Flow Tube Mass Spectrometry[J]. BioMed Central.2008,1:41.
[26]Z H Endre, J W Pickering. Breath ammonia and trimethylamine allow real-time monitoring of haemodialysis efficacy[J]. Physiological Measurement.2011,32(1): 115-130
[27]Wolfgang Singer, Jens Herbig, Rene Gumann. Applications of PTR-MS in Medicine and Biotechnology[J]. Life Science Solutions.2011
[28]Ulrich Riess, Uwe Tegtbur. Experimental setup and analytical methods for the non-invasive determination of volatile organic compounds, formaldehyde and NOx in exhaled human breath[J]. Analytica Chimica Acta.2010,53-62
[29]J King, PMochalski. Dynamic profiles of volatile organic compounds in exhaled breath as determined by a coupled PTR-MS/GC-MS study[J]. Physiol. Meas.2010,31: 1169-1184
[30]K. Okamura, T. Ishi ji, M. Iwaki, Y. Suzuki, K. Takahashi. Electrochemical gas sensor using a novel gas permeable electrode modified by ion implantation [J]. Surface and Coatings Technology.2007,201:8116-8119.
[31]A. D.Wilson, M. Baietto. Advances in Electronic-Nose Technologies Developed for Biomedical Applications[J]. Sensors.2011,11:1105-1176.
[32]Reinhard Fend, et al. Monitoring haemodialysis using electronic nose and chemometrics[J]. Biosensors and Bioelectronics,2004,119:1581-1590
[33]Haick H, Hakim M, Patrascu M, Levenberg C, Shehada N, Nakhoul F, Abassi Z. Sniffing chronic renal failure in rat model by an array of random networks of single-walled carbon nanotubes[J]. ACS Nano.2009,3(5):1258-1266
[34]P. Montuschi, M. Santonico. Diagnose performance of an electronic nose, fractional exhaled nitric oxide and lung function testing in asthma[J]. Chest 2010,137, 790-796.
[35]Perena Gouma, Krithika Kalyanasundaram, Xiao Yun. Nanosensor and Breath Analyzer for Ammonia Detection in Exhaled Human Breath [J]. IEEE SENSORS JOURNAL.2010,10(1): 49-53.
[36]V. H. Tran, P. C. Hiang, M. Thurston, P. S. Thomas, et al. Breath analysis of lung cancer patients using an electronic nose detection system[J]. IEEE Sens. J.2010, 10 (9):1514-1518.
[37]Wang Ping, Tan Yi, et al. A novel method for diabetes diagnosis based on electronic nose [J]. Biosensors & Bioelectronics.1997,12 (9-10):1031～1036
[38]胡卫军,王平,杨成忠,胥媛.仿生光学人工鼻及其呼吸气体检测的实验研究[J].中国生物医学工程学报,2006,25(1)：51-57
[39]王乐,王镝,王平.基于谐振型SAW传感器的呼吸监测系统设计[J].传感技术学报,2011,24(4)：498-502
[40]S. Persijn, F. Harren, A.vanderVeen. Quantitative gas measurements using a versatile OPO-based cavity ringdown spectrometer and the comparison with spectroscopic databases[J]. Appl. Phys. B.2010,100(2):383-390.
[41]J. Wojtas, Z. Blelecki, T. Stacewicz, J. Stacewicz, Ultra sensitive laser spectroscopy for breath analysis. Opto-Electron. Rev.2012.20(1):26-39.
[42]V. Spagnolo, A. A. Kosterev, L. Dong, R. Lewicki, F. K. Tittel. NO trace gas sensor based on quartz-enhanced photoacoustic spectroscopy and external cavity quantum cascade laser[J]. Appl. Phys. B.2010,100(1):125-130.
[43]F. J. M. Harren, R. Berkelmans, K. Kuiper, S. te Lintel Hekkert, P. Scheepers, R. Dekhuijzen. On-line laser photoacoustic detection of ethane in exhaled air as biomarker of ultraviolet radiation damage of the human skin[J]. Applied Physics Letters,1999,74(12):1761-1763.
[44]C. Roller, K. Namjou, J. Jeffers, et al. Simultaneous NO and C02 measurement in human breathwith a single IV-VImid-infrared laser[J]. Optics Letters.2002, 27 (2):107-109.
[45]C. Roller, K. Namjou, J. D. Jeffers,et al. Nitric oxide breath testing by tunable-diode laser absorption spectroscopy:Application in monitoring respiratory inflammation[J]. Applied Optics.2002,41 (28):6018-6029.
[46]M. M. Baum, S. Kumar, A. M. Lappas, et al. Measurement of acetylene in breath by ultraviolet absorption spectroscopy:Potential for noninvasive cardiac output monitoring[J]. Review of Scientific Instruments.2003,74(6):3104-3110.
[47]C. J. Wang, S. T. Scherrer, D. Hossain. Measurements of cavity ringdown spectroscopy of acetone in the ultraviolet and near-infrared spectral regions:Potential for development of a breath analyzer[J].Applied Spectroscopy.2004,58(7):784-791.
[48]K. D. Skeldon, C. A. Wyse, S. D. Monk. Application of laser spectroscopy for measurement of exhaled ethane in patients with lung cancer [J]. Respiratory Medicine.2006,100 (2): 300-306.
[49]T. Hibbard, A. J. Killard. Breath ammonia level in a normal human population study as determined by photoacoustic laser spectroscopy[J]. Journal of Breath Research. 2011,5(3):1-8.
[50]D. D. Arslanov, Koen Swinkels, S. M. Cristescu, F. J. M. Harren. Real-time, subsecond, multicomponent breath analysis by Optical Parametric Oscillator based Off-Axis Integrated Cavity Output Spectroscopy [J]. Opt Express.2011,19(24)-.24078-24089.
[51]C. Patel. Sensitive Analysis of Breath Gases for "Bloodless Blood Tests" [J]. Gases and Technology,2002,1:24-30.
[52]C. Kumar Patel, Eric Mueller. Optical-nose technology competes with breath analyzers and blood test[J]. Laser Focus With Fiberoptic Technology.2002,38(11) 83-84,86,88.
[53]Hibbard, Troy, Killard, Anthony. Breath ammonia analysis:Clinical application and measurement[J]. Critical Reviews in Analytical Chemistry.2011,41(1):21—35.
[54]Hiroyuki Wakabayashi, Yoshihiro Kuwabara, Hiroyuki Murata,et al. Measurement of the Expiratory Ammonia Concentration and its Clinical Significance [J]. Metabolic Brain Disease.1997,12(2):161-169.
[55]S. Davies, P. Spanel, D. Smith. Quantitative analysis of ammonia on the breath of patients in end-stage renal failure [J]. Kidney International.1997,52:223-228.
[56]Ricardo Claps, F. V. Englich, F. K. Tittel, et al. Ammonia detection by use of near-infrared diode-laser-based overtone spectroscopy[J]. Applied Optic.2001, 40(24):4387-4394.
[57]L. Narasimhan, W. Goodman, C. Patel. Correlation of breath ammonia with blood urea nitrogen and creatinine during hemodialysis [J], Proceedings of the National Academy of Sciences of the United States of America,2001,98:4617-4621.
[58]Kearney D J, Hubbard T, Putnam D. Breath Ammonia Measurement in Helicobacter pylori Infection[J]. Digestive Diseases and Sciences.2002,47(11):2523-2530.
[59]A. M. Diskin, P. Spanel, D. Smith. Time variation of ammonia, acetone, isoprene and ethanol in breath:a quantitative SIFT-MS study over 30 days [J]. Physiological Measurement.2003,24:107-119.
[60]Suja DuBois, Sue Eng, Renuka Bhattacharya, et al. Breath Ammonia Testing for Diagnosis of Hepatic Encephalopathy[J]. Digestive Diseases and Sciences.2005, 50(10):1780-1784.
[61]Kei Toda, Jianzhong Li, Purnendu K. Dasgupta. Measurement of ammonia in human breath with a liquid-film conductivity sensor[J]. Anal. Chem.2006,78:7284-7291.
[62]J. Manne,0. Sukhorukov, W. Jager, J. Tulip. Pulsed quantum cascade laser-based cavity ring-down spectroscopy for ammonia detection in breath[J], Applied Optics, 2006,45:9230-9237
[63]Patrik Spanel, Kseniya Dryahina, David Smith. Acetone, ammonia and hydrogen cyanide in exhaled breath of several volunteers aged 4-83 years [J]. J. Breath Res. 2007,1(1):1-4.
[64]H. Ishida, T. Satou, K. Tsu ji, N. Kawashima, H. Takemura, Y. Kosaki, S. Shiratori, T. Agishi. The breath ammonia measurement of the hemodialysis with a QCM-NH3 sensor[J]. Bio-Medical Materials and Engineering.2008,18:99-106.
[65]Katherine T. Moorhead. Modelling Acute Renal Failure using Blood and Breath Biomarkers inRats[J]. The 7th IFAC Symposium on Modelling and Control inBiomedical Systems.2009.144-150
[66]P. Gouma, K. Kalyanasundaram, X. Yun, M. Stanacevic, L. S. Wang. Nanosensor and Breath Analyzer for Ammonia Detection in Exhaled Human Breath[J]. IEEE Sensors Journal. 2010,10:49-53.
[67]D. C. Dumitras, D. C. Dutu, C. Matei, et al. Evaluation of Ammonia Absorption Coefficients by Photoacoustic Spectroscopy for Detection of Ammonia Levels in Human Breath[J]. Laser Physics.2001,214:796-800.
[68]Giovanni Neri, Antonio Lacquaniti,Giuseppe Rizzo. Real-time monitoring of breath ammonia during haemodialysis:use of ion mobility spectrometry(IMS) and cavity ring-down spectroscopy(CRDS) techniques[J]. Nephrology Dialysis Transplantation. 2012,0:1-8.
[69]A. G. Bell. On the production and reproduction of sound by light[J]. Am. J. Sci. 1880,20:305-324.
[70]M. L. Viegerov. Eine Methode der GAsanalyse, Beruhend auf der Optisch-Akustischen Tyndall-Rontegeners-cheinung[J].Dokl. Akad. Nauk SSSR.1938,19:687-688.
[71]K. Luft. Uber eine neue methode der registrierenden gasanalyse mit hilfe der absorption ultraroter strahlen ohne spektrale zerlegung[J]. Zeitschrift Fur Technische Physik.1943,24:97-104.
[72]G. Gorelik. On a possible method of studying energy exchange times between the different degrees of freedom of molecules in a gas [J]. Dokl. Akad. Nauk SSSR,1946, 54:779.
[73]E. L. Kerr, J.G. Atwood. The Laser Illuminated Absorptivity Spectrophone:A Method for Measurement of Weak Absorptivity in Gases at Laser Wavelengths[J], Applied Optics,1968,7:915-921.
[74]L. B. Kreuzer. Ultralow gas concentration infrared absorption spectroscopy[J]. Journal of Applied Physics.1971,42:2934.
[75]C. N. Patel, E. G. Burkhardt, C. A. Lambert. Spectroscopic Measurements of Stratospheric Nitric Oxide and Water Vapor[J]. Science.1974,184:1173-1176.
[76]张望.光声光谱微量气体检测技术及其应用研究[D]：(博士学位论文).大连：大连理工大学,2010.
[77]F. G. C. Bijnen, J. Reuss, F. J. M. Harren. Geometrical optimization of a longitudinal resonant photoacoustic cell for sensitive and fast trace gas detection[J]. Review of Scientific Instruments.1996,67:2914-2923.
[78]M. A. Gondal. Laser photoacoustic spectrometer for remote monitoring of atmospheric pollutants [J]. Applied Optics.1997,36:3195-3201.
[79]M. W. Sigrist, A. Bohren, T. von Lerber, et al. Environmental applications of laser-based photoacoustic spectroscopy[J]. Analytical Sciences.2001, 17:S511-S514.
[80]D. Marinov, M. W. Sigrist. Monitoring of road-traffic emissions with a mobile photoacoustic system [J]. Photochemical & Photobiological Sciences.2003,2:774-778.
[81]M. Gianella, J. M. Rey, D. Hahnloser, M. W. Sigrist. C02 laser-photoacoustic analysis of smoke emitted during minimal invasive electro-knife surgery[J]. Eur. Phys. J.2008, Special Topics 153,459-462.
[82]http://www.pranalytica.com/technology-gas-sensors
[83]M. B. Pushkarsky, M.E.Webber, C. K. N. Patel. Ultra-sensitive ambient ammonia detection using C02-laser-based photoacoustic spectroscopy[J]. Applied Physics B-Lasers and Optics.2003,77:381-385.
[84]http://www.ru.nl/tracegasfacility/trace_gas_research/laser_spectroscopy/
[85]S. M. Cristescu, S. T. Persuijn, S. TE Lintel Hekkert, F. J. M. Harren. Laser-based system for trace gas detection in life sciences. Appl. Phys. B.2008,92:343-349.
[86]F. Kuhnemann, K. Schneider, A. Hecker, A. Martis, W. Urban, S. Schiller, J. Mlynek. Photoacoustic trace-gas detection using a cw single-frequency parametric oscillator[J]. Applied Physics B:Lasers and Optics,1998,66:741-745.
[87]C. Fischer, M. Sigrist, Q. Yu, M. Seiter. Photoacoustic monitoring of trace gases by use of a diode-based difference frequency laser source [J]. Optics Letters,2001, 26:1609-1611
[88]T. L. Wee.J. Ng, A. H. Kung, A. Miklos, P. Hess. Trace gas detection of C2H4 by photoacoustic spectroscopy using a compact pulsed optical parametric oscillator [J].J. Phys. IV France.2005,125:597-599
[89]D. D. Arslanov, K. Swinkels, S. M. Cristescu, F. J. M. Harren. Real-time, subsecond, multicomponent breath analysis by Optical Parametric Oscillator based Off-Axis Integrated Cavity Output Spectroscopy[J].Opt. Express.2011,19:24078-24089.
[90]Z. Bozoki, A. Mohacsi, G. Szabo, Z. Bor, M. Erdelyi, W. D. Chen, F. K. Tittel. Near-infrared diode laser based spectroscopic detection of ammonia:A comparative study of photoacoustic and direct optical absorption methods [J], Applied Spectroscopy,2002,56:715-719.
[91]A. Schmohl, A. s. M. s, P. Hess. Detection of ammonia by photoacoustic spectroscopy with semiconductor lasers[J]. Applied Optics.2002,41:1815-1823.
[92]M. E. Webber, M. Pushkarsky, C. K. N. Patel. Fiber-amplifier-enhanced photoacoustic spectroscopy with near-infrared tunable diode lasers[J]. Applied Optics,2003,42:2119-2126.
[93]J. P. Besson, S. Schilt, L. Thevenaz. Sub-ppb ammonia detection based on photoacoustic spectroscopy [J].17th International Conference on Optical Fibre Sensors, Pts 1 and 2,2005,5855:415-418.
[94]Rafat Lewicki, Anatoliy A. Kosterev, David M. Thomazy, F. K. Titte. Real Time Ammonia Detection in Exhaled Human Breath using a distributed feedback quantum cascade laser based sensor [J]. Proc.of SPIE.2011,7945:50K-2
[95]B. A. Paldus, T. G. Spence, R. N. Zare, J. Oomens, F. J. M. Harren. Photoacoustic spectroscopy using quantum-cascade lasers [J], Optics Letters,1999,24:178-180.
[96]A. Mukherjee, M. Prasanna, M. Lane, R. Go, I. Dunayevskiy, A. Tsekoun, C. K. N. Patel. Optically multiplexed multi-gas detection using quantum cascade laser photoacoustic spectroscopy [J], Applied Optics,2008,47:4884-4887
[97]V. Spagnolo, A. A. Kosterev, L. Dong, R. Lewicki, F. K. Tittel. NO trace gas sensor based on quartz enhanced photoacoustic spectroscopy and external cavity quantum cascade laser[J]. App. Phys.B.2010,100:125-130.
[98]A. A. Kosterev, Y. A. Bakhirkin, R. F. Curl, F. K. Tittel. Quartz-enhanced photoacoustic spectroscopy [J], Optics Letters,2002,27:1902-1904.
[99]A. A. Kosterev, F. K. Tittel. Ammonia detection by use of quartz-enhanced photoacoustic spectroscopy with a near-IR telecommunication diode laser [J], Applied Optics,2004,43:6213-6217.
[100]Raf at Lewicki, A. A. Kosterev, Y. A. Bakhirkin, D. M. Thomazy, F. K. Titte, et al. Real Time Ammonia Detection in Exhaled Human Breath with a Quantum Cascade Laser Based Sensor[J]. Conference on Lasers and Electro-Optics (CLEO).2009.
[101]L. Dong,A. A. Kosterev, D. Thomazy, F. K. Tittel. Compact Portable QEPAS Multi-gas Sensor[J]. Proc. of SPIE.2011,7945:50R-1.
[102]J. Fonsen, V. Koskinen, K. Roth, J. Kauppinen. Dual cantilever enhanced photoacoustic detector with pulsed broadband IR-source[J]. Vibrational Spectroscopy.2009,50(2):214-217.
[103]C. B. Hirschmann, N. S. Koivikko, J. Raittila, et al. FT-IR-cPAS—New Photoacoustic Measurement Technique for Analysis of Hot Gases:A Case Study on VOCs[J]. Sensors(Basel).2011,11(5):5270-5289.
[104]C. N. Patel. Laser Photoacoustic Spectroscopy Helps Fight Terrorism:High Sensitivity Detection of Chemical Warfare Agent and Explosives[J]. The European Physical Journal.2008,Special Topics 153:1-18.
[105]http://www. omnisens.ch/vl/tga/251-tgaproducts. php
[106]http://www. innova-airtech. com/
[107]Liusan Wang, Zhensong Cao, Xiaoming Gao,et al.A widely tunable(5-12.5u m) continuous-wave mid-infrared laser spectrometer based on difference frequency generation in AgGaS2[J]. Optics Communications.2011,284:358-362.
[108]JingsongLi, X. Gao, W. Li, et al. Near-infrared diode laser wavelength modulation-based photoacoustic spectrometer[J]. Spectrochimica Acta Part A.2006, 64:338-342.
[109]K.Liu, J. Li, L. Wang, F. K. Tittel. Trace gas sensor based on quartz tuning fork enhanced laser photoacoustic spectroscop [J].Appl Phys B.2009,94:527-533.
[110]Hongming Yi, Kun Liu, Weidong Chen, et al. Application of a broadband blue laser diode to trace N02 detection using off beam quartz enhanced photoacoustic spectroscopy[J]. Optics Letters.2011,36(4):481-483.
[111]于清旭,王艺,刘中凡,林钧岫.双能级跃迁cO激光器腔内光声光谱测量[J].大连理工大学学报.1995,35：258-262.
[112]于清旭,林钧岫,尤斯·欧文斯,弗朗·斯哈伦.用激光光声检测技术研究乙醛对苹果乙烯产量的影响[J].大连理工大学学报.1999,39：498-503.
[113]Y. Peng, W. Zhang, L. Li, Q. X. Yu. Tunable fiber laser and fiber amplifier based photoacoustic spectrometer for trace gas detection[J]. Spectrochimica Acta Part a-Molecular and Biomolecular Spectroscopy.2009,74:924-927.
[114]刘善峥,张望,于清旭.基于可调谐掺铒光纤激光器和掺铒光纤放大器的光声光谱气体分析仪[J].中国激光.2009,36：964-967.
[115]Q. Y. Wang, J. W. Wang, Q. X. Yu. An all-optical photoacoustic spectrometer for trace gas detection[J]. Sensors and Actuators B-Chemical.2011,153:214-218.
[116]李洪艳.基于光声光谱技术的多组分气体检测系统研究[D].秦皇岛：燕山大学电气工程学院,2010.
[117]陈伟根,周恒逸,黄会贤,唐炬.基于半导体激光器的乙炔气体光声光谱检测及其定量分析[J].仪器仪表学报.2010,31(3)：665-670.
[118]王建业,纪新明,黄宜平等.光声光谱法探测微量气体[J].传感技术学报.2006,19(4)：1206-1211.
[119]http://www. xmzsh. com/.../2011年世界肾脏日宣传册(中华医学会肾脏病学分会编).doc
[120]肖月,隋宾艳,赵琨.我国终末期肾病现状及透析技术的应用、费用及支付情况分析[J].中国卫生政策研究.2011,4：29-33.
[121]USRDS 2011 Annual Data Report:Atlas of Chronic Kidney Disease and End-Stage Renal Disease in the United States, National Institutes of Health[R]. National Institute of Diabetes and Digestive and Kidney Diseases,2011.
[122]A. Singla, M. J. Antonino, K. P. Bliden,et al.The relation between platelet reactivity and glycemic control in diabetic patients with cardiovascular disease on maintenance aspirin and clopidogrel therapy[J]. American Heart Journal.2009, 158:784-784.
[123]Ligor,Tomasz. Analytical Methods for Breath Investigation[J]. Critical Reviews in Analytical Chemistry.2009,39(1):2-12
[124]A. Amann, et al. Breath analysis for medical diagnosis and therapeutic monitoring[J]. Spectroscopy Europe.2005,17(3):18-20.
[125]王宗明,何欣翔,孙殿卿.实用红外光谱学[M]：石油工业出版社,1990.
[126]李民赞.光谱分析技术及其应用[M]：科学出版社,2006.
[127]周炳琨,陈倜嵘.激光原理[M]：国防工业出版社,2009.
[128]陆同兴,路轶群.激光光谱技术原理及应用[M]：中国科学技术大学出版社,1999.
[129]J. P. BESSON. Photoacoustic spectroscopy for multi-gas sensing using near infrared lasers[D]. Lausanne:Swiss Federal Institute of Technology(EPFL),2006.
[130](美国)罗森威格著,王耀俊等译.光声学和光声谱学[M].北京：科学出版社,1986.
[131]殷庆瑞等著.光声光热技术及其应用[M].北京：科学出版社,1991
[132]刘善峥.基于光纤激光器和光纤放大器的光声光谱仪[D]：(硕士学位论文).大连：大连理工大学,2009.
[133]J. Reid, D. Labrie. Second-harmonic detection with tunable diode lasers—Comparison of experiment and theory[J]. Applied Physics B:Lasers and Optics.1981, 26(3):203-210.
[134]杨晓龙.光声光谱技术中的多气体成份分析方法研究[D]：(硕士学位论文).大连：大连理工大学,2003.
[135]张嵩.基于光声光谱技术的多组分气体检测方法研究[D]：(硕士学位论文).重庆：重庆大学,2007.
[136]P. G. Blake. Practical guide to measuring adequacy of dialysis [J]. Advances in renal replacement therapy.1999,6(1):80-84.
[137]J. S.Lee循环与呼吸系统中的物质传输[M]：重庆大学出版社,1993.
[138]李良.人体呼出氨气的光声光谱检测技术研究[D]：(硕士学位论文).大连：大连理工大学,2010.
[139]杨乐平,李海涛,肖相生.LabView程序程序设计与应用[M].北京：电子工业出版社,2005.
[140]Herzberg G.分子光谱与分子结构[M].北京：科学出版社,1983.
[141]HITRAN and PNNL Database, http://savi. weber. edu/hi_plot/index. html
[142]M. E. Webber, D. S. Baer, R. K. Hanson. Ammonia monitoring near 1.5μm with diode-laser absorption sensors[J].Applied Optics.2001,40(12):2031-2042.